Proactive monitoring of adalimumab trough concentrations in children was associated with higher corticosteroid-free sustained remission and biologic remission rates compared with reactive monitoring in pediatric patients with Crohn disease (CD), according to the results of a study published in Gastroenterology.
Pediatric inflammatory bowel disease is increasingly managed with biologic agents. Proactive monitoring of drug trough concentrations and antibodies against drugs may help determine whether patients are likely to respond to treatment and increase efficacy.
Children with CD were recruited at 9 pediatric gastroenterology units in Israel between July 2015 and December 2018 to investigate whether proactive drug monitoring is associated with higher rates of clinical remission. The primary endpoint was sustained corticosteroid-free clinical remission at all visits (weeks 4 and 8 and then every 8 weeks until week 72).
Biologic-naive children (n=78; mean age, 14.3 years; range 6-18 years; female, 29%) who had responded to adalimumab induction therapy under scheduled monitoring for clinical and biologic measures were randomly assigned (1:1) to 2 groups: proactive monitoring of trough concentrations (n=38) or reactive monitoring (after loss of response; n=40). Adalimumab dosage was adjusted to achieve trough concentrations of 5 mg/mL for all patients.
Sustained corticosteroid-free clinical remission was achieved by 82% of children (31/38) in the proactive group and 48% children (19/40) in the reactive group (P =.002). A composite outcome (of sustained corticosteroid-free remission, C-reactive protein £0.5 mg/dL, and level of fecal calprotectin £150 mg/g) was achieved by 42% of patients in the proactive monitoring group (16/38) compared with 12% of patients in the reactive monitoring group (5/40; P =.003). At the 72-week timepoint, more patients in the proactive monitoring group (87% [33/38]) had received adalimumab intensification than in the reactive monitoring group (60% [24/40]; P =.001).
The rate of adverse events (AEs) was low (18% [14/38]), and adalimumab treatment was considered well tolerated. The 2 monitoring groups did not differ in the incidence of AEs. Serious AEs that resulted in treatment termination occurred in 2 patients of the proactive monitoring group (pancreatitis and peripheral neuropathy).
The study was limited by a small sample size and the nonblinded design. It also failed to include therapeutic drug monitoring measurement during induction or endoscopic evaluation at enrollment and end of study.
The authors concluded, “These results could assist physicians to improve care of pediatric patients with CD, particularly in achieving a better control of inflammatory activity.”
Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Assa A, Matar M, Turner D, et al. Proactive monitoring of adalimumab trough concentration associated with increased clinical remission in children with Crohn’s disease compared with reactive monitoring. Gastroenterology. 2019 Oct; 157(4):985-996.e2.